Patent GB-566788-A (GB)
Title: Manufacture of sulphonamides
IPC: C07D239/69
Filed: 1942-07-07
Abstract: Sulphonamides of therapeutic value are obtained by reacting a heterocyclic amine containing at least one nitrogen atom in the ring with a compound of the general formula <FORM:0566788/IV/1> where R-SO2 represents the residue of a sulphonic acid, the sulpho group of which is linked to a carbon atom not forming part of an aromatic ring.  R1 represents an amino group or a substituent convertible into an amino group by hydrolysis or reduction and X represents the remaining members of a thiazole or a thiodiazole ring.  When R1 is not an amino group, the reaction product is subjected to hydrolysis or reduction. Specified values for R1 are acylamino, nitro and azo groups. The group R may be an aliphatic, araliphatic, alicyclic or heterocyclic residue.  Heterocyclic amines which are specified for use in the above reaction include aminopyridines, aminothiazoles, aminothiodiazoles, aminopyrimidines, or aminopyrazines such as 2-aminopyridine, 2-aminothiazole, 2-amino-4-methyl thiazole, 2-amino-4 : 5-dihydrothiazole, 2-amino-4-oxo-5-ethyl-4 : 5-dihydrothiazole, 2-amino-5-methyl-thiodiazole, 2-amino-5-ethyl-thiodiazole, 2-aminopyrimidine, 2-amino-4-methyl-pyrimidine, 2-amino-4 : 6-dimethylpyrimidine, 6-amino-2 : 4-dimethylpyrimidine, and 2 - amino - pyrazine.  The reaction is conducted in a solvent such as pyridine or quinoline, and preferably at a raised temperature.  In examples: (1) 2-(benzylsulphonamido) - 3 - (p - acetylaminobenzenesulphonyl)-thiazoline is reacted with aminothiazole in pyridine solution to give on making strongly acid a precipitate of 2-benzylsulphonamidothiazole.  On neutralization of the acid mother liquor, there is obtained 2-(p-aminobenzenesulphonamido)-thiazole. Alternative starting materials to give the same final product are mentioned.  (2) The same starting material as in example (1) is reacted with 2-amino-5-methylthiodiazole in pyridine solution to give 2-(p-aminobenzenesulphonamido) - 5 - methyl - thiodiazole. Alternative heterocyclic amines which may be used are 2-aminopyrimidine, 6-amino-2 : 4 - dimethyl - pyrimidine, 2 - amino - pyridine, or 2-amino-pyrazine.  (3) The same thiazoline starting material as in example (1) is reacted with 2-amino-4 : 6-dimethyl pyrimidine in pyridine solution to give 2-(p-aminobenzenesulphonamido) - 4 : 6 - dimethyl - pyrimidine. (4) The same thiazoline starting material as in example (1) is reacted with 2-amino-4-methyl pyrimidine in pyridine solution to give 2-(p-aminobenzenesulphonamido) - 4 - methyl pyrimidine.  2 - (Benzylsulphonimido) - 3 - (p - acetylaminobenzenesulphonyl)-thiazoline is prepared by condensing 2-amino thiazole with benzene sulphonic acid chloride in the presence of pyridine to form 2 - benzylsulphonamido - thiazole and reacting this in alkaline aqueous acetone with p-acetylaminobenzene sulphochloride.  2-Benzylsulphonamido - 5 - methyl - thiodiazole-(1 : 3 : 4) is prepared by condensing 2-amino-5-methyl-thiodiazole-(1 : 3 : 4) with benzyl sulphochloride in pyridine solution. 2-Ethylsulphonamidothiazole is prepared by condensing 2-aminothiazole with ethane sulphochloride in pyridine solution.  2 - (Benzylsulphonamido) - 3 - (p - nitrobenzenesulphonyl)-thiazoline is prepared by condensing 2 - benzylsulphonamidothiazole with p - nitrobenzenesulphochloride in the presence of alkali.  A sample has been furnished under Sect. 2 (5) of the acts of 2-(p-aminobenzenesulphonamido) pyridine prepared as follows: 2-amino-5-methylthiodiazole-(1 : 3 : 4) is condensed with benzyl sulphochloride in pyridine to give 2-benzylsulphonamido - 5 - methyl thiodiazole - (1 : 3 : 4) which is treated in aqueous alkaline acetone solution with p-acetylaminobenzene sulphochloride to form 2-(benzylsulphonimido)-3-(p-acetylaminobenzenesulphonyl) - 5 - methyl thiodiazoline-(1 : 3 : 4).  This compound is heated with 2-amino-pyridine in pyridine solution to give the required product. The Specification as open to inspection under Sect. 91 describes also the use as starting materials 2- or 6-aminopyrimidines containing as substituents two sulphonic acid residues.  As the heterocyclic amine component there may be used any heterocyclic amine compound.  This subject-matter does not appear in the Specification as accepted.